Chronic Bronchitis Acute Exacerbation

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Acute exacerbations of chronic bronchitis may be triggered by bacterial or viral infection or may be noninfectious. H. influenzae accounts for 50% of bacterial exacerbations with S. pneumoniae and M. catarrhalis causing an additional third (Moussaoui et al., 2008). For acute exacerbation of COPD associated with purulent sputum and increased shortness of breath, antibiotic therapy decreases mortality by 77% and treatment failure by 53% (Ram et al., 2009). This finding was true regardless of the antibiotic choice, although coverage for the organisms just noted seems rationale. Consideration of the frequency of beta-lactamase production within these organisms in a community is important. More recent meta-analysis shows that a shorter course, no longer than 5 days, is as effective as longer treatment with antibiotic (Moussaoui et al., 2008).

Other features of the management of acute exacerbation of chronic bronchitis include systemic corticosteroids, inhaled beta agonists and anticholinergics (e.g., ipratropium), and support for oxygenation status and ventilation. Patients with chronic bronchitis may have multiple hospital admissions and may remain colonized with both community-acquired and hospital-acquired organisms. It is advisable to reserve the use of antibiotics, unless absolutely necessary to prevent the development of resistant organisms.

KEY TREATMENT

Antibiotics for the treatment of bronchitis is not recommended because of the cost, potential for side effects, and lack of clinical benefit (Braman, 2006; Smith et al., 2009) (SOR: A). In the treatment of Bordetella pertussis, early administration of a mac-rolide antibiotic and patient isolation will likely decrease coughing paroxysms and limit spread of disease (Braman, 2006) (SOR: A). In adults with acute bronchitis with signs of airway obstruction, as evidenced by wheezing on examination or decreased peak expiratory flow rate, beta-2 agonists may be helpful in alleviating cough (Braman, 2006) (SOR: B).

For acute exacerbation of COPD associated with purulent sputum and increased shortness of breath, treatment with antibiotics decreases mortality by 77% and treatment failure by 53% (Ram et al., 2009) (SOR: A).

PNEUMONIA

Anthony Zeimet

Key Points

• Assessment tools for pneumonia severity (e.g., CURB-65) can help determine the treatment approach.

• The therapy of pneumonia is often empiric because the infecting organism is not readily isolated in more than 50% of cases.

• Chest radiography is one of the most useful diagnostic tools in pneumonia.

Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma and, along with influenza, is the seventh leading cause of death in the United States. Fever, cough, sputum production, pleuritic chest pain, and dyspnea are common symptoms of CAP. Nausea, vomiting, and diarrhea also may occur, and in elderly patients, CAP may present with mental status changes. Although its absence usually makes pneumonia less likely, fever can be absent in the elderly patient. Other physical examination findings include an elevated respiratory rate, conversational dyspnea, tachycardia, and rales. Egophony and dullness to percussion may be noted with focal consolidation. Typical laboratory findings include leukocytosis. The diagnosis of pneumonia is based on the presence of symptoms and the presence of an infiltrate on chest radiograph. If infiltrate is not present, consider obtaining a chest tomography scan (which has higher sensitivity) to rule in or rule out CAP. If negative, other diagnoses should be considered.

The most common microbiologic agent of pneumonia is often not isolated (Table 16-1). Furthermore, studies have shown that bacteriologic causes of pneumonia cannot be determined by radiographic appearance (i.e., "typical" vs. "atypical"). In the proper clinical setting, certain clinical microbes should be considered because they can affect treatment considerations and epidemiologic studies. These include Legionella spp., influenza A and B, and community-acquired methicillin-resistant Staphylococcus aureus (MRSA).

Certain diagnostic tests are performed based on clinical setting. Blood cultures are not routinely done in the outpatient setting but should always be done if the patient is being admitted to the hospital, ideally before antibiotics are given. The use of Gram stain and sputum culture remains controversial but can provide more evidence of a bacterial cause (e.g., many PMNs). If sputum cultures are being obtained, it is recommended that the physician have the patient expectorate directly into a specimen cup and have it sent immediately for processing. This can increase the yield of isolating Streptococcus pneumoniae among

Table 16-1 Most Common Etiologies of Community-Acquired Pneumonia

Patient Type

Etiology

Outpatient

Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses"

Inpatient (non-ICU)

S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae Legionella spp. Aspiration Respiratory viruses"

Inpatient (ICU)

S. pneumoniae Staphylococcus aureus Legionella spp. Gram-negative bacilli H. influenzae

Modified from Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society-American Thoracic Society Consensus Guidelines on Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis 2007;44:S27-S72. ICU, Intensive care unit.

*Influenza A and B, adenovirus, respiratory syncytial virus, and parainfluenza.

other respiratory pathogens. Other tests include urine antigen tests for S. pneumoniae, Legionella pneumophila serogroup 1, and nasal swab for influenza A and B. In young children, RSV, adenovirus, and parainfluenza in addition to influenza are common causes. Nasal swab for RSV and influenza can be rapidly done, but the other causes can be determined with viral cultures, serology, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR), although results usually are received after resolution of the acute symptoms.

Perhaps the most important decision for clinicians is to determine the location of treatment. The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) recommend use of the pneumonia severity index (PSI), which uses 20 variables to risk-stratify the patient into five mortality classes, or the CURB-65, which measures five clinical variables in this decision making. The CURB-65 may be the easiest and most convenient to use at the site of decision making. A score of 0 or 1 indicates treatment as an outpatient; a score of 2 requires hospital admission to the general medical ward; and a score of 3 or more indicates admission to an intensive care unit (ICU) (Box 16-1).

Treatment of CAP should be targeted toward the most likely etiology (Table 16-2). Outpatient therapy for patients who have no comorbidities and have not received antibiotics within the last 3 months includes doxycycline or a macrolide antibiotic. Use of a fluoroquinolone antibiotic (levofloxacin or moxifloxacin) should be reserved for patients with more complicated pneumonia and those requiring hospitalization. Patients who have comorbid conditions or recent antibiotic exposure, or who will be hospitalized, should receive a respiratory fluoroquinolone or combination therapy with a beta-lactam drug plus a macrolide, for 48 to 72 hours after fever abates (usually 5-7 days' total therapy). If an organism is isolated, therapy may be narrowed to cover the causative agent. The clinician should consider longer therapy and appropriate antibiotics to cover for infection by less common organisms such as Staphylococcus aureus or Pseudomonas aeruginosa. If the patient has no more than one abnormal value (temperature <37.8° C, heart rate <100, respiratory rate <24, SBP >90, O2 saturation >90%, Po2 >60 on room air) and the patient is able to maintain oral intake and has a normal mental status, the clinician can safely switch to oral therapy and discharge the patient from the hospital. Unless the etiology of the pneumonia is known, the physician should switch to oral antibiotics in the same class as the intravenous antibiotics used.

Box 16-1 CURB-65 Criteria

Assign a value of 1 for each variable:

• Confusion: Is the patient disoriented to person, place, or time?

• Respiratory rate > 30 breaths/min

• Blood pressure: systolic <90 or diastolic <60 mm Hg

Interpretation

• Score 0 or 1: outpatient treatment

• Score 2 : inpatient treatment on a general medical floor

• Score >3: inpatient treatment in an intensive care unit

BUN, Blood urea nitrogen.

The U.S. Preventive Services Task Force (USPSTF) along with IDSA and ATS recommend annual influenza vaccinations to those over 50 years of age, those who are (or who reside with those who are) at high risk for influenza complications, and all health care workers. Furthermore, the pneumococcal vaccine should be given to all those over age 65. Smoking cessation is also important and should be discussed at each clinic visit.

KEY TREATMENT

Locally adapted guidelines should be implemented to improve the processing of care variables and relevant clinical outcomes in pneumonia (Mandell et al., 2007) (SOR: B). Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the patient's ability to take oral medication safely and reliably and the availability of outpatient support resources (Mandell et al., 2007) (SOR: B).

For patients with CURB-65 score of 2 or higher, more intensive treatment (i.e., hospitalization or, where appropriate and available, intensive in-home health care services) is usually warranted (Mandell et al., 2007) (SOR: C).

INFLUENZA

Anthony Zeimet

Key Points

• Concerns about development of resistant seasonal and H1N1 swine-derived influenza virus should be considered in the decision to administer antiviral medications to healthy patients with these infections.

• The abrupt onset of fever with chills, headache, malaise, myalgias, arthralgias, and rigors during "flu season" is sufficient to diagnose influenza.

• Prevention of influenza is generally with vaccination.

Influenza deserves special mention because it is an important cause of pneumonitis and can precede a bacterial pneumonia. Influenza viruses are medium-sized enveloped ribonucleic acid (RNA) viruses that consist of a lipid bilayer with matrix proteins with spiked surface projections of glycoproteins (hemagglutinins, neuraminidase) on the outer surface (Figure 16-1). Both influenza A and influenza B have eight segmented pieces of single-stranded RNA. The only difference between influenza A and B is that B does not have an M2 ion channel. Hemagglutinins, three types of which typically infect humans (H1, H2, H3), bind to respiratory epithelial cells and allow fusion with the host cell. Neuraminidase, consisting of two types (N1, N2), allows release of virus from the infected cells.

A unique aspect of influenza is that antigenic variation occurs annually. Antigenic shift is caused by a genetic reas-sortment between animal and human influenza strains, producing a novel virus that generally causes the worldwide pandemics. Influenza viruses circulate mostly among humans, birds, and swine. Sometimes; a human strain and an animal strain can intermingle and create a new, unique virus. This is what happened during spring 2009, heralding the most recent pandemic and creating "Novel H1N1 Influenza" (swine influenza). Genotype analysis

Table 16-2 Guide to Empiric Choice of Antimicrobial Agent for Treating Patients with Community-Acquired Pneumonia (CAP)

Patient

Characteristics Preferred Treatment Options

Outpatient

Previously Healthy

No recent antibiotic Oral-based p-lactam, macrolide," or therapy doxycycline

Recent antibiotic therapyt A respiratory fluoroquinolone^ alone, an advanced macrolide" plus high-dose amoxicillin,5 or an advanced macrolide plus high-dose amoxicillin-clavulanate.1

Comorbidities (COPD, diabetes, renal failure or congestive heart failure, or malignancy)

No recent antibiotic An advanced macrolide" plus p-lactam or a therapy respiratory fluoroquinolone

Recent antibiotic therapy A respiratory fluoroquinolone^ alone or an advanced macrolide plus a p-lactam""

Suspected aspiration with Amoxicillin-clavulanate or clindamycin infection

Influenza with bacterial Vancomycin, linezolid, or other coverage superinfection for MRSA or community-acquired MRSA

Inpatient

Medical Ward

No recent antibiotic A respiratory fluoroquinolone alone or an therapy advanced macrolide plus a p-lactamn

Recent antibiotic therapy An advanced macrolide plus a p-lactam, or a respiratory fluoroquinolone alone (regimen selected will depend on nature of recent antibiotic therapy)

Data from Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27-S72.

COPD, Chronic obstructive pulmonary disease; MRSA, methicillin-resistant Staphylococcus aureus. "Azithromycin or clarithromycin.

fThat is, the patient was given a course of antibiotic(s) for treatment of any infection within the past 3 months, excluding the current episode of infection. Such treatment is a risk factor for drug-resistant Streptococcus pneumoniae and possibly for infection with gram-negative bacilli. Depending on the class of antibiotics recently given, one or another of the suggested options may be selected. Recent use of a fluoroquinolone should dictate selection of a nonfluoroquinolone regimen, and vice versa.

¿Moxifloxacin, levofloxacin, or gemifloxacin.

5Dosage: 1 g orally (PO) three times daily (tid).

1Dosage: 2 g PO twice daily (bid).

""High-dose amoxicillin (1 g tid), high-dose amoxicillin-clavulanate (2 g bid), cefpodoxime, cefprozil, or cefuroxime.

^Cefotaxime, ceftriaxone, ampicillin-sulbactam, or ertapenem.

¿¿The antipseudomonal agents chosen reflect this concern. Risk factors for Pseudomonas infection include severe structural lung disease (e.g., bronchiectasis) and recent antibi otic therapy, health care-associated exposures or stay in hospital (especially in the ICU). For patients with CAP in the ICU, coverage for S, pneumoniae and Legionella species must always be considered. Piperacillin-tazobactam, imipenem, meropenem, and cefepime are excellent p-lactams and are adequate for most S, pneumoniae and H, influenzae infections. They may be preferred when there is concern for relatively unusual CAP pathogens, such as P, aeruginosa, Klebsiella spp., and other gram-negative bacteria. 55Piperacillin, piperacillin-tazobactam, imipenem, meropenem, or cefepime. ##Data suggest that older adults receiving aminoglycosides have worse outcomes. "Dosage for hospitalized patients, 750 mg/day.

Patient

Characteristics

Preferred Treatment Options

Intensive Care Unit (ICU)

Pseudomonas infection is not an issue

A p-lactamtt plus either an advanced macrolide or a respiratory fluoroquinolone

Pseudomonas infection is not an issue but patient has a ß-lactam allergy

A respiratory fluoroquinolone, with or without clindamycin

Pseudomonas infection is an issued (cystic fibrosis, impaired host defenses)

Either (1) an antipseudomonal p-lactam55 plus ciprofloxacin, or (2) an antipseudomonal agent plus an aminoglycoside* plus a respiratory fluoroquinolone or a macrolide

Pseudomonas infection is an issue but the patient has a ß-lactam allergy. Health care-associated exposure

Aztreonam plus aminoglycoside plus levofloxacin11 or other respiratory quinolone

Anti-Pseudomonas cephalosporin, carbapenem (not ertapenem) or p-lactam/p-lactamase inhibitor with anti-Pseudomonas activity plus vancomycin (for MRSA coverage) ± quinolone or aminoglycoside

Nursing Home

Receiving treatment in nursing home

A respiratory fluoroquinolone alone or vancomycin (for 5. aureus including MRSA) plus a ß-lactam (cefepime or piperacillin/ tazobactam if Pseudomonas is suspected; ceftriaxone if Pseudomonas is not suspected)

Hospitalized

Same as for medical ward and ICU

of this strain determined that components came from an influenza virus circulating among swine herds in North America that combined with a virus circulating among ill swine in Eurasia, creating a new influenza strain capable of causing disease in humans. Because this virus had not previously infected humans, it had the potential to cause widespread morbidity and mortality worldwide. During pandemics, the U.S. Centers for Disease Control and Prevention (CDC) estimates an additional 10,000 to 40,000 deaths caused by influenza. Although higher than in non-pandemic years, mortality was significantly less than initially predicted in 2009.

Neuraminidase Hemagglutinin

Viral Gene segment envelope -RNA

-Nucleoprotein -Polymerase proteins

M1 protein

Table 16-3 Common Cold versus Influenza Symptoms

M1 protein

M2 Protein

Figure 16-1 Schematic model of influenza A virus.

(From Treanor JJ: Influenza viruses, including avian influenza and swine influenza. In Mandell GL, Bennett JE, Dolin RD (eds). Mandell, Douglas, and Bennett's Principles and Practices of Infectious Diseases, 7th ed. Philadelphia, Churchill Livingstone, 2010, p 2266.)

Table 16-3 Common Cold versus Influenza Symptoms

Symptom

Common Cold

Influenza

Fever

Rare

Abrupt onset

Cough

Frequent, usually hacking

Frequent, usually severe

Sore throat

Frequent

Rare

Nasal congestion

Frequent

Rare

Sneezing

Frequent

Rare

Myalgia

Rare

Frequent

Headache

Rare

Frequent

Fatigue

Mild

Severe

Figure 16-1 Schematic model of influenza A virus.

(From Treanor JJ: Influenza viruses, including avian influenza and swine influenza. In Mandell GL, Bennett JE, Dolin RD (eds). Mandell, Douglas, and Bennett's Principles and Practices of Infectious Diseases, 7th ed. Philadelphia, Churchill Livingstone, 2010, p 2266.)

The abrupt onset of fever, along with chills, headache, malaise, myalgias, arthralgias, and rigors during "flu season," is sufficient to diagnose influenza. As the fever resolves, a dry cough and nasal discharge predominate. A rapid nasal swab or viral cultures can be used to confirm the diagnosis of influenza but is rarely needed. In fact, the sensitivity of these rapid tests can range from 50% to 70%, so a negative test does not rule out influenza. The primary care physician needs to determine if the patient has influenza or the common cold, because symptoms of both illnesses generally overlap (Table 16-3).

Treatment of influenza is generally not necessary because it is usually a self-limiting condition. Treatment should be reserved for those with comorbidities who present within 48 hours of symptom onset. Neuraminidase inhibitors (zana-mivir and oseltamivir) prevent the release of virus from the respiratory epithelium and are approved for both influenza A and influenza B. The M2 inhibitors (amantadine and rimantadine) are approved by the U.S. Food and Drug Administration (FDA) for the treatment of influenza A because these drugs block the M2 ion protein channel, preventing fusion of the virus to host cell membrane (influenza B has no M2 ion channel). The use of M2 inhibitors is limited because of increasing resistance among influenza A viruses, as well as causing central nervous system (CNS) problems that are usually exacerbated in elderly persons, who are more likely to seek treatment for influenza (Table 16-4).

The major complication of influenza is a secondary bacterial pneumonia or exacerbation of underlying COPD. Initial improvement in clinical symptoms followed by deterioration usually suggests a secondary bacterial pneumonia, which can usually be confirmed with a chest radiograph showing an infiltrate. Other, less common complications of influenza include myositis, myocarditis, pericarditis, transverse myelitis, encephalitis, and Guillain-Barre syndrome.

Prevention of influenza is generally with vaccination. Box 16-2 outlines patients at risk for influenza complications who should be vaccinated yearly. Although anyone wanting an influenza vaccine should be vaccinated, during periods of vaccine shortage, high-risk groups have priority. A well-matched vaccine can prevent influenza among 70% to 90% of adults and decrease work absenteeism. Conversely, a poorly matched vaccine only prevents influenza in 50% of healthy adults. Proper hand hygiene and covering one's cough are two additional important components in preventing the spread of influenza virus.

KEY TREATMENT

Early treatment (within 48 hours of onset of symptoms) with oseltamivir or zanamivir is recommended for influenza A (Jefferson et al., 2006) (SOR: A).

Use of oseltamivir and zanamivir is not recommended for patients with uncomplicated influenza with symptoms for more than 48 hours (Kaiser and Hayden, 1999) (SOR: A).

Oseltamivir and zanamivir may be used to reduce viral shedding in hospitalized patients or to treat influenza pneumonia (Mandell et al., 2007) (SOR: C).

SYSTEMIC VIRAL INFECTIONS

Anthony Zeimet

Key Points

Population-based vaccination programs have been highly effective in decreasing the incidence of many viral infections. Acyclovir can be used in adults and children with varicella to decrease symptoms if given in the first 48 hours after rash onset, but its benefit must be weighed against its cost and the possibility of development of viral resistance.

Antiviral medications should be considered to decrease the incidence of postherpetic neuralgia, particularly in older patients.

Box 16-2 Groups at risk for Influenza Complications*

Table 16-4 Treatment and Chemoprophylaxis Recommendations for Influenza

Agent/ Group

Treatment

Chemoprophylaxis

Neuraminidase Inhibitors

Oseltamivir

Adults

75-mg capsule twice daily (bid) for 5 days

75-mg capsule once daily (qd)

Children (age >12 mo)

<15 kg

60 mg/day divided into 2

doses

30 mg qd

15-23 kg

90 mg/day in 2 doses

45 mg qd

24-40 kg

120 mg/day in 2 doses

60 mg qd

>40 kg

160 mg/day in 2 doses

75 mg qd

Zanamivir

Adults

Two 5-mg inhalations (10 mg bid)

Two 5-mg inhalations (10 mg qd)

Children

Two 5-mg inhalations (10 mg bid)(age >7 yr)

Twp 5-mg inhalations (10 mg qd)(age >5 yr)

M2 Inhibitors (Adamantadines)*

Rimantadine1

Adults

200 mg/day as either a single daily dose or divided into 2 doses

200 mg/day as either a single daily dose or divided into 2 doses

Children

1-9 yr

6.6 mg/kg/day (max, 150 mg/day) divided in 2 doses

5 mg/kg qd, not to exceed 150 mg

>10 yr

200 mg/day as either a single daily dose or divided into 2 doses

200 mg/day as either a single daily dose or divided into 2 doses

Amantadine

Adults

200 mg/day as either a single daily dose or divided into 2 doses

200 mg/day as either a single daily dose or divided into 2 doses

Children

1-9 yr

5-8 mg/kg/day divided into 2 doses or as a single daily dose (max, 150 mg/day)

5-8 mg/kg/day divided into 2 doses or as a single daily dose (max, 150 mg/day)

2 doses

Modified from Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management. Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-1032.

*The amantadines should be used only when influenza A (H1N1) infection or exposure is suspected. The amantadines should not be used for infection or exposure to influenza A (H2N3) or influenza B.

Rimantadine has not been approved by the U.S. Food and Drug Administration for treatment of children, although published data exist on safety and efficacy in the pediatric population.

Unvaccinated infants age 12 to 24 months

Persons with asthma or other chronic pulmonary disease, such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults

Patients with hemodynamically significant cardiac disease Patients with immunosuppressive disorders or receiving immunosup-pressive therapy

Patient with human immunodeficiency virus (HIV) infection Patients with sickle cell anemia and other hemoglobinopathies Patients with disease requiring long-term aspirin therapy (e.g., rheumatoid arthritis, Kawasaki disease) Patients with chronic renal obstruction Patients with cancer

Patients with chronic metabolic disease, such as diabetes mellitus Patient with neuromuscular disorders, seizure disorders, or cognitive dysfunction that may compromise the handling of respiratory secretions

Adults older than 66 years

Residents of any age of nursing homes or other long-term care facilities

Modified from Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management. Clinical Practice Guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-1032.

*Data suggest that the highest risk of both mortality and serious morbidity (e.g., hospitalization) occurs in severely immunocompromised patients (e.g., hematopoietic stem cell transplant patients) and very elderly (>85 years) residents of nursing homes; infants under age 24 months also have high hospitalization rates but lower case-fatality rates than the other two groups.

• Measles has had a resurgence in recent years and should be suspected when a patient presents with cough, coryza, conjunctivitis, and head-to-toe rash.

• Epstein-Barr virus and cytomegalovirus infections are generally not clinically distinguishable, and their treatment is primarily supportive.

Vaccinations have dramatically decreased the incidence of a number of historically common viral infections; smallpox has been eradicated through widespread vaccination. However, recent outbreaks of measles and mumps on college campuses underscore the need to remain vigilant in administering vaccines at the population level, even though no vaccine is available for many common viruses.

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